Hypothalamus-Pituitary-Adrenal Hyperactivity in Human Aging Is Partially Refractory to Stimulation by Mineralocorticoid Receptor Blockade | Zendy

Roberta Giordano | Zendy; Mario Bo | Zendy; Micaela Pellegrino | Zendy; Marco Vezzari | Zendy; Matteo Baldi | Zendy; Andreea Picu | Zendy; M. Balbo | Zendy; Lorenza Bonelli | Zendy; Giuseppe Migliaretti | Zendy; Ezio Ghigo | Zendy; Emanuela Arvat | Zendy

Open Access

Hypothalamus-Pituitary-Adrenal Hyperactivity in Human Aging Is Partially Refractory to Stimulation by Mineralocorticoid Receptor Blockade

Author(s) -

Roberta Giordano,

Mario Bo,

Micaela Pellegrino,

Marco Vezzari,

Matteo Baldi,

Andreea Picu,

M. Balbo,

Lorenza Bonelli,

Giuseppe Migliaretti,

Ezio Ghigo,

Emanuela Arvat

Publication year - 2005

Publication title -

the journal of clinical endocrinology and metabolism

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.206

H-Index - 353

eISSN - 1945-7197

pISSN - 0021-972X

DOI - 10.1210/jc.2005-0105

Subject(s) - endocrinology , medicine , glucocorticoid , mineralocorticoid , adrenocorticotropic hormone , hydrocortisone , placebo , mineralocorticoid receptor , vasopressin , hypothalamic–pituitary–adrenal axis , glucocorticoid receptor , dehydroepiandrosterone , psychology , hormone , aldosterone , androgen , alternative medicine , pathology

Context: The hypothalamus-pituitary-adrenal (HPA) axis is mainly regulated by CRH, arginine vasopressin, and glucocorticoid feedback. Hippocampal mineralocorticoid receptors mediate proactive glucocorticoid feedback and mineralocorticoid antagonists, accordingly, stimulate HPA axis. Age-related HPA hyperactivity reflects impaired glucocorticoid feedback at the suprapituitary level. Design: ACTH, cortisol, and dehydroepiandrosterone (DHEA) secretion were studied in eight healthy elderly (75.1 ± 3.2 yr) and eight young (25.0 ± 4.6 yr) subjects during placebo or canrenoate (CAN) administration (200 mg iv bolus followed by 200 mg infused over 4 h). Results: During placebo administration, ACTH and cortisol areas under the curve (AUCs) in elderly subjects were higher than in young subjects (P ≤ 0.01); conversely, DHEA AUCs in elderly subjects were lower than in young subjects (P = 0.002). CAN increased ACTH, cortisol, and DHEA levels in both groups. In young subjects, ACTH, cortisol, and DHEA levels at the end of CAN infusion were higher (P ≤ 0.05) than after placebo. In elderly subjects, at the end of CAN infusion, ACTH, cortisol, and DHEA levels were higher (P = 0.01) than after placebo. Under CAN, ACTH and cortisol AUCs were persistently higher (P ≤ 0.01) and DHEA AUCs lower (P = 0.006) in elderly than in young subjects. Cortisol AUCs after CAN in young subjects did not become significantly different from those in elderly subjects after placebo. Conclusions: 1) Evening-time ACTH and cortisol secretion in elderly subjects is higher than in young subjects; 2) ACTH and cortisol secretion in elderly subjects is enhanced by CAN but less than that in young subjects; and 3) DHEA hyposecretion in elderly subjects is partially restored by mineralocorticoid antagonism. Age-related variations of HPA activity may be determined by some derangement in mineralocorticoid receptors function at the hippocampal level.

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